In the 1980 USGP at Carlsbad , Danny Chandler ran the only-stroke in the open class. Always wondered what it was. I thought it was a Honda though. Was the HL motor a one off or is it a modified TT500 motor?

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Honda 750 Four (the grand daddy of mass production superbikes)
Kawasaki GPz1100 (the grand daddy of the mass production sportbikes)
Kawasaki 500/750 Triple (the grand daddy of "hold my beer" speed/power category)
Honda Goldwing + GL1800 (the grand daddy, the bloodline, and the reigning king of ultimate touring bike class)
BMW "R" series motorcycles (the grand-daddies of functional motorcycles for the masses)

I'd say at the top of the list for all, is the 69 Honda CB750. Because it changed SO many facets of motorcycling:
High performance
Reasonable cost
Reliability
Serviceability
Adaptability
Features (disc brakes, electric starting, etc).

But I feel it is the bike, because it brought all these aspects together in a package SO many riders could afford, modify and really enjoy.

This is why it should be #1 on the list

1969 - Imagine coming back from a run and not having to tighten bolts, or maybe go back and look for that muffler that vibrated off.

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There may be other brands that sold in higher quantities, but I bet the aggregate R-bike miles are higher - both from a individual bike as well as total across the group. Hence my nomination in the "functional" category. 15 year old R-bikes can respectfully be discussed as "low miles" if they have < 100k miles...

Honda 750 Four (the grand daddy of mass production superbikes)
Kawasaki GPz1100 (the grand daddy of the mass production sportbikes)
Kawasaki 500/750 Triple (the grand daddy of "hold my beer" speed/power category)
Honda Goldwing + GL1800 (the grand daddy, the bloodline, and the reigning king of ultimate touring bike class)
BMW "R" series motorcycles (the grand-daddies of functional motorcycles for the masses)

I agree with a lot of this but this may be the first time I've ever seen someone refer to a BMW motorcycle as being "for the masses." If I were going to pick a motorcycle for most significance in the category of functional motorcycle for the masses, it would have to be the Honda Super Cub, no question.

Gee, all these bikes listed and not a single vote for one of the most significant bikes, the Velocette KTT series?

KTT MK I - positive stop foot change gearbox and an engine with high RPM, narrow power band. Basically the prototype for all modern motorcycles.

KTT MK VIII - just to have to include this one, one of the best looking race bikes ever, swing arm suspension that actually worked, magnesium bits on the factory bikes, gas charged shocks (on the factory bikes), and very successful on track. All this in the late 1930's! This bike was even raced postwar with some success.

My definition of "significant" (which the OP left open to interpretation, so I think for most folks it's just another version of "favorite, "best", etc.) is the fundamental impact it had on the industry. I don't know enough about real old bikes that pioneered some technology first, but let's say there are 6 of them, whatever they were, up through the 1965 or so. For the remaining 6 I'd chose:

1) 1967 Yamaha DT1- for making the genre broad base affordable and reliable
2) 1969 Honda CB750- for all the known reasons
3) 1972 H-D Superglide- something has to function as the seminal cruiser: after all, they are 50% of the US market. So I'd nominate this because it's considered the first factory custom.
4) 1980 Honda Gold Wing GL1100- first Japanese/mass market bike outfitted as a touring bike from the factory that demonstrated that "touring bikes" could be their own market segment (case could be made for the original 1974 GL1000)
5) 1980 Ducati Pantah 500SL- Without this bike (specifically the engine design) there would be no Ducati as we know it today. And nothing for the rest to catch up to.
6) 1985 Suzuki GSX-R750, a reset on sport biking that has been the design model ever since.

Honorary mention to early Yamaha production racers (RD/TZs from 250-750)-- quantities of quality race bikes for the masses certainly had an impact.

In reviewing this list I'm really struck that they're all "old" bikes. There's probably a few new bikes I'm not thinking of, but I'm really struggling to think of ones that aren't some variation or logical extension of the 6 I named.